Infection by human papillomaviruses (HPV) at specific epithelium cells to induce epithelial proliferations plays an important role for cervical carcinogenesis. About 99 percent of confirmed cervical cancer cases are found to be associated with HPV infection with biopsy-confirmed squamous intraepithelial lesions (SIL) or cervical intraepithelial neoplasia (CIN). The incidence of HPV infection, primarily transmitted through sexual contact, is highest among young women and about 20 million sexually active men and women worldwide are currently infected.
In addition to cervical cancer, the presence of HPV DNA has been detected in tumor tissues of head and neck cancer, oral cancer, esophageal cancer, and some skin cancers, as well as lung cancer and colorectal cancer. The detection of HPV DNA in colorectal cancer tissues by in situ hybridization and PCR suggested that HPV infection might be associated with the carcinogenesis of colorectal cancer. However, HPV DNA was not detectable by regular PCR in one earlier study and a survey of HPV16 virus-like particle (VLP) antibodies in patients with epithelial cancers also failed to provide an association of HPV with colorectal cancer challenging the association of colorectal cancers with HPVs. However, colorectal HPV infection is common in patients with colorectal cancer, albeit at a low DNA copy number, with HPV16 being the most prevalent type. The inconsistent results may come from the issues of assay sensitivity for HPV detection. HPV infection may play a role in colorectal carcinogenesis. More sensitive assays for detection of HPV in colorectal cancer are required to demonstrate the association of HPV with carcinogenesis of colorectal cancer.
Some genital malignancies like vulvar or cervical neoplasms are associated with previous infection with human papillomavirus (HPV). Because of vicinity of bladder to mucosal surface of urogenital tract, HPV may play a significant role in transitional cell carcinoma (TCC). The etiology of TCC, which represents 90 percent of bladder malignancies, is not quite clear, while squamous cell carcinoma (5%) of the bladder is well associated with some factors like urinary stones and prolonged infections. HPV detection rate in clinical samples of invasive cervical cancer can be as high as 99%. Recently, conflicting findings have been reported on association of HPV infection and TCC. Using PCR techniques to detect human papillomavirus (HPV), HPV DNA can be observed prevalently in about 40% to 45% of penile carcinoma clinical samples, about 45% of vulvar carcinoma, and some bladder malignancies.
Methods of detecting HPV infection with nucleic acid methods, such as “DNA Hybrid Capture”, have been developed. However, they are not ideal, not only due to its high cost, assay operation procedures, the requirements for facility, equipment, and highly trained personnel, but also its very low positive predictive value to CIN. In addition, DNA testing could not differentiate the diagnosis of LSIL from HSIL, or CIN lesions from non-transforming latent or remissive viral infection. What is needed is a low cost, simple, sensitive and specific assay that can be performed routinely in a clinical lab or doctor's office and is capable of detecting early stages of epithelial lesions, distinguishing LSIL from HSIL, or predicting the risk of progression into cervical cancer.
Thus, there is a need to detect whether HPV proteins are expressed in a variety of carcinomas and cancers, and determine whether HPV proteins play any role in the progression of the different types of carcinomas/cancers; and if so, which HPV proteins are important in these carcinomas/cancers.